title: Is aristolochic acid nephropathy a widespread problem in developing countries? A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical-phytochemical approach.
abstract: BACKGROUND
  Species of Aristolochia are associated with aristolochic acid nephropathy (AAN), a renal interstitial fibrosis and upper urinary tract cancer (UUC). Aristolochic acid nephropathy has been reported in ten countries but its true incidence is unknown and most likely underestimated. By combining an ethnobotanical and phytochemical approach we provide evidence for the risk of AAN occurring in Bangladesh. More specifically, we assess the intra-specific variation of aristolochic acid analogues in medicinally used Aristolochia indica samples from Bangladesh.
  
  
  METHODS
  Ethnobotanical information was collected from 16 kavirajes (traditional healers) in different study locations in Bangladesh. Plant samples were obtained from native habitats, botanical gardens, herbal markets and pharmaceutical companies. The samples were extracted using 70% methanol and were analysed using LC-DAD-MS and (1)H-NMR.
  
  
  RESULTS
  Roots as well as leaves are commonly used for symptoms such as snake bites and sexual problems. Among the informants knowledge about toxicity or side effects is very limited and Aristolochia indica is often administered in very high doses. Replacement of Aristolochia indica with other medicinal plants such as Rauvolfia serpentina (L.) Benth. ex Kurz was common. Aristolochia indica samples contained a variety of aristolochic acid analogues such as aristolochic acid I, aristolochic acid II, cepharadione A and related compounds.
  
  
  CONCLUSIONS
  AAN cases are likely to occur in Bangladesh and more awareness needs to be raised about the health risks associated with the use of Aristolochia indica and other species of Aristolochia as herbal medicines.
authors.affiliation: Centre for Pharmacognosy and Phytotherapy, UCL School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Johanna
authors.initials: J
authors.lastname: Michl
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Jennings
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Kite
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Ingrouille
authors.forename: Monique S J
authors.initials: MS
authors.lastname: Simmonds
authors.forename: Michael
authors.initials: M
authors.lastname: Heinrich
mesh_terms: D030022:Aristolochia / Q000737:chemistry*; D034341:Aristolochic Acids / Q000302:isolation & purification / Q000627:therapeutic use / Q000633:toxicity*; D001459:Bangladesh / Q000453:epidemiology; D003906:Developing Countries; D019448:Ethnobotany; D020834:Ethnopharmacology; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000453:epidemiology; D012306:Risk
chemical_list: D034341:Aristolochic Acids; C000228:aristolochic acid I
keywords: 3-(tetramethylsilyl)propionic-2,2,3,3-d4 acid, sodium salt; A; AA; AAA; AAN; AL; Aristolochia indica; Aristolochic acid; BA; BEN; Balkan endemic nephropathy; Bangladesh; COSY; CP; D(2)O; EBC; ESI; GNP; HMBC; HMQC; J-RES; J-resolved; K(2)HPO(4); KH(2)PO(4); Kidney; LC-DAD-MS; LC-MS; MS; MeOD; Metabolomics; NMR; NOESY; PC; PCA; PPM; PTFE; RBG; RPM; Royal Botanic Gardens, Kew; S; TSP; Toxicity; UUC; UV; alstonine; aristolactam; aristolochic acid; aristolochic acid analogue; aristolochic acid nephropathy; benzoic acid; commercial product; correlation spectroscopy; deuterated methanol; deuterated water; di-potassium hydrogen orthophosphate; economic botany collection; electrospray ionisation; gross national product; heteronuclear multiple-bond correlation spectroscopy; heteronuclear multiple-quantum correlation spectroscopy; liquid chromatography-diode array detector-mass spectrometry; liquid chromatography-mass spectrometry; m/z; market sample; mass-to-charge-ratio; nuclear Overhauser effect spectroscopy; nuclear magnetic resonance; parts per million; polyfluoroethylene; potassium dihydrogen orthophosphate; principle component; principle component analysis; retention time; revolutions per minute; serpentine; t(R); ultraviolet; upper urinary tract cancer